Genetic warfare Genetic mutations in mitochondria, inherited from the mother, are an important cause of male infertility, a new study in fruit flies has found.

Evolutionary biologist Dr Damian Dowling of Monash University in Melbourne and colleagues report their findings today in the journal Science.

"What we've uncovered here is an evolutionary process that can explain why male infertility is so common," says Dowling. "Our study is essentially the first evidence for the 'mothers curse'".

One in 20 men are infertile but the causes are largely unknown.

Medical researchers have long suspected that the powerhouse of cells, mitochondria, could play a role in male infertility, given that sperm rely on the energy of mitochondria to power their race to the egg.

In recent years some evolutionary biologists suggested that male infertility and other male-specific diseases could result from an accumulation of mutations in the maternally-inherited mitochondria.

According to this hypothesis the quality of mitochondrial genes is screened only by natural selection acting on females, which means there is no weeding out of mutations that are only bad for males, not for females.

"It predicts that the mitochondria will be a hot spot for mutations that affect male fertility," says Dowling.

Experiment

Dowling and colleagues carried out an experiment to test this "mothers curse" idea.

They gathered mitochondrial DNA from a diverse range of fruit flies around the world and inserted it into flies that had identical nuclear DNA.

The researchers then looked at the expression of over 10,000 nuclear genes in individual male and female flies.

They found that the different mitochondrial DNA affected the expression of about a 1000 nuclear genes in males, but had no effect on the same genes in females.

"The maternal transmission of the mitochondrial genome results in a process which we call the sex-specific selective sieve - mutations are getting through the sieve of natural selection," says Dowling.

He says one in every 10 male nuclear genes had their expression increased or decreased.

"The top 300 of these differentially expressed genes are located within the male testes or in the glands that are responsible for producing the ejaculate," says Dowling.

"It basically points firmly at the idea that males harbour this load of mutations within the mitochondria that are all teaming up to effect male fertility in a detrimental way."

Battle of the sexes

But, it's not all doom and gloom, says Dowling.

His team found suggestions that the male nuclear genome comes up with adaptations that counter this lost fertility brought on by the mitochondria.

"What we suspect is that we have this co-evolutionary arms race between mitochondrial genomes and nuclear genomes," he says.

"The mitochondrial genes take the side of the females and the nuclear genes take the side of the males."

Implication for humans

Dowling says the genome of a fly is very similar to those of a human, particularly when it comes to the mitochondria.

And he says the new findings suggest that mitochondrial gene mutations are a much more important cause of human male infertility than previously considered.

Dowling hopes medical researchers will now focus more on the role of mitochondria in male infertility.

"We hope to have provided them with a roadmap of where they should be looking," he says.